Biomaterials for MEMS

Chapter Nine

Vibration-based Anti-Biofouling of

Implants

Po Ying Jacob Yeh

∗,‡

, Jayachandran N. Kizhakkedathu

†

and Mu Chiao

∗,§

∗

Department of Mechanical Engineering, 2054-6250 Applied Science Lane,

University of British Columbia, Vancouver, B.C., Canada.

‡

E-mails: [e-mail],

§

[e-mail]

†

Centre for Blood Research and Department of Pathology and Laboratory Medicine,

4th Floor, Life Sciences Centre, 2350 Health Sciences Mall, University of British

Columbia, Vancouver, B.C., Canada.

E-mail: [e-mail]

The interfacial behavior of proteins at surfaces has attracted much attention over the

years because of the problem of fouling, which is encountered in implants, microfiltar-

tion membrane, medical implantable devices, drug delivery system and biosensors.

A novel anti-biofouling mechanism based on the combined effects of electric field

and shear stress is reported. The mechanism was observed in mm scale piezoelectric

plates coated with different metal materials and MEMs (MicroElectroMechanical

system) fabricated membrane based device. Experimental observation of quantity

of proteins adsorption and theoretical calculations of protein-surface interactions

(van der Waals (VDW), electrostatic, and hydrophobic) and shear stress reveal the

mechanism for protein desorption from surface. This anti-fouling mechanism is also

able to implant to micromachined MEMs membrane. The dimension of membrane

(Si(2 μm)/SiO

2

(1 μm)) is 2000 μm × 500 μm × 3 μm. The membrane vibrates in a

flexural plate wave (FPW), which is further verified by finite element simulation. The

surface charges on the membrane and the fluid shear stress contribute in attenuating

the protein adsorption on the membrane surface. Potentially, a microelectromechani-

cal system (MEMS)-based vibrating membrane could be a tool to minimize biofouling

of in vivo implants.

9.1 INTRODUCTION

The success of implantable device technologies, such as artificial joint, vascu-

lar graft, cardiopacemaker, cardiovascular, drug delivery system, and biosensor,

Biomaterials for MEMS, Edited b y M. Chiao and J.-C. Chiao

Copyright © 2011 by Pan Stanford Publishing Pte. Ltd.

www.panstanford.com

978-981-4241-46-5

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204 P. Y. J. Yeh, J. N. Kizhakkedathu and M. Chiao

had improved the patients’ life quality. However, with the advances of these

technologies, the view of biocompatibility had extended from the “the host tol-

erates the device” to “the device tolerates the host and vice versa”.

1,2

For example,

a subcutaneous glucose sensor comprises of immobilized enzymes, electrodes and

a semi-permeable membrane. The semi-permeable membrane acts as a protecting

layer that keeps the enzyme and electrodes from the attack of the immune system

and it allows glucose from interstitial space to diffuse through. In order to be

successful, the semi-permeable membrane must not induce pathogenic reactions

to the host. On the other hand, the glucose permeability of the membrane must be

maintained at all times. Hence, the problem of biofouling needs to be reduced as

much as possible.

Biofouling is a process started immediately after a foreign object comes into

contact with biological fluids because of the immune response system. And it is

considered to be one of the greatest challenges of medical implantation.

2−5

The

immediate response is to flood the injured area with blood followed by adsorption

of blood proteins onto the implant surface and activation of the molecular and

cellular defense systems.

6,7

The coagulation, complement, immune and inflamma-

tory pathways can all be initiated by this process as can platelet and white cell

activation. The extent to which these responses occur depends on the nature of

the protein adsorption, specific binding or rejection reactions that occur at the

impalnt-blood interface. Usually an adsorbed protein layer of thickness from

0.5 to 9 μm accumulates over time. Approximately 21 days after implantation,

an avascular fibrous capsule of up to 100 μm will form around the implant and

may reduce its performance.

8

Prevention of protein adsorption unto implants

is critical for increasing their longevity. Some methods had been provided so

far, such as polymer-based coatings,

9−19

plasma surface functionalization,

20

sur-

face charges,

21

detergent coatings,

22

nano-structured surfaces,

8

surface roughness

and topography,

23,24

mechanical vibration,

8,25−27

and flow flushing upon the

surface,

28,29

etc. Coatings, surface roughness, surface topography are catalogued

as passive methods, while physical means, such as mechanical vibration and flow

flushing are considered as active methods of anti-biofouling.

Numerous studies have indicated that the surface chemistry of and

microstructure on the implant surface can modulate protein adsorption.

3,4,8,30

And

among those passive methods, polymer coating is attractive for certain applica-

tions, such as long-circulating sterically protected liposome,

31

biosensor,

32

and

protein chip.

33

Those polymer candidates usually are composed by three parts,

anchor to surface, monomer repeated backbone, and end functional group.

The most popular polymer used is probably the hydrophilic poly(ethylene gly-

col) (PEG). When there is sufficient high PEG graft density, the coiled PEG with one

end anchored to the surface will form brushes by extending the coils away from

surface, and so that to create a steric barrier from protein adsorption.

34,35

However,

polymer coatings are successful for short term and often fail in the case of a

highly complex mixture of proteins, for example, blood plasma,

9,13

or under in vivo

conditions.

5

As an alternative to polymer coating, researchers have also fabricated

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